الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Excess calorie intake, especially from a diet high in fat, is a risk factor for both obesity and reproductive abnormalities. High-fat diet (HDF) consumption has been linked to ovarian dysfunction and shorten the reproductive life span of the female, resulting in premature ovarian insufficiency (POI). Treatment of this condition with pharmaceutical drugs could have side effects. Now, many studies have attempted to find treatment from natural products and medicinal plants that have no side effects and are safer than drugs. from the common medicinal plants and natural products are salvia officinalis and bee bread, which have powerful antioxidant, anti-inflammatory, and estrogenic activities.
So this study was designed to study the effects of HFD on ovarian function and evaluate the potential role of both S. officinalis, bee bread, and shifting of HFD to a normal diet in alleviating HFD-induced ovarian dysfunction and to elucidate the underling mechanisms through their effects on the reproductive hormones, steroidogenesis, folliculogenesis, estrous cycle regularity, inflammation (systematically, locally), autophagy, apoptosis (caspase-3), PPAR𝛾�, lipid profile, blood glucose, and bodyweight.
The study was performed on 38 females Wistar albino rats (4 weeks old) weighing about 80–85 g, were randomly assigned and divided into five groups. The control group (n = 7) received the normal diet (ND) for 14 weeks. The HFD group (n = 10) received a high-fat diet for ten weeks. After 10 weeks, 3 rats were randomly selected and sacrificed at the diestrus stage, while the other 7 female rats proceeded to the end of the experiment and were sacrificed at the 14th week. HFD + S. officinalis extract group (n = 7): rats were given HFD for ten weeks; after the 10th week, they received HFD with S. officinalis extract (300 mg/kg b.w.t./day) via oral gavage for an additional 4 weeks. While the HFD+ bee bread group (n = 7) were given HFD for ten weeks and after the 10th week they received HFD with bee bread (0.5 g/kg b.w.t./day) via oral gavage for an additional 4 weeks. Finally, HFD/ND group (n = 7) rats were given HFD for ten weeks, and after the 10th week, they shifted from the HFD to the normal diet for an additional 4 weeks.
Body weight was recorded weekly at the 10th and 14th weeks, the estrous cycle was evaluated in all groups. By the end of the 14th week, all rats were sacrificed when they were at the diestrus stage. Ovarian tissues were harvested and weighed; blood was collected. The ovarian CCDN1, ATG5 and CYTP17A1 and the blood TNFα, and IL-6 relative mRNA expression levels were analyzed by qRT-PCR. The serum level of reproductive hormones was measured using ELISA and the lipid profile and fasting blood glucose level were determined using the spectrophotometric method. The histopathological changes evaluation and immunohistochemical examinations of NFκB, PPAR𝛾�and caspase-3 were done using light microscopy.
The results of the present study revealed the following:
The HFD group showed a significant increase in body weight, blood glucose, lipid profile, and increased relative mRNA expression of inflammatory genes (TNFα, IL-6) in the blood, while the ovarian NFκB showed strong immunohistochemical expression. The levels of reproductive hormones were severely impaired in the HFD group with increased irregularity in the estrous cycle. Histopathological findings revealed a decrease in the ovarian reserve (decrease in the number of primordial follicles), a decrease in the number and diameter of the corpus luteum, and an appearance of cystic follicles. Also, there was an increase in inflammatory cell infiltration and an increase in fat vacuole appearance. Immunohistochemical analysis showed strong expression of caspase-3 and weak expression of PPAR𝛾�. All these changes impairing the ovarian function and reproductive life span in female rats.
Bee bread and S. officinalis administration revealed improvement in molecular, biochemical, histological, and immunohistochemical alterations in ovaries induced by HFD feeding. They led to a significant decrease in body weight, blood glucose, lipid profile, and relative mRNA expression of TNF-α and IL-6. Also, they improved the reproductive hormones and increased the regularity of the estrous cycle. Also, the histopathological and immunohistochemical changes improved as there were an increase in the number of primordial follicles and the of corpus luteum, the absence of cystic follicles and decreased the infiltration of inflammatory cells and fat vacuole presence. The immunohistochemical examinations showed that increase expression of PPAR𝛾� and decreased expression of NFκB and caspase-3 when compared with the HFD group.
The HFD/ND group also revealed improvements in HFD-induced ovarian dysfunction as it resulted in a decrease in the bodyweight, blood glucose, lipid profile, and relative mRNA expression of TNFα and IL-6. improve the reproductive hormones and increase the regularity of the estrous cycle. Also, the histopathological and immunohistochemical changes improved as they revealed an increase in primordial follicles and the number of corpus luteum and a decrease in the appearance of cystic follicles. decreased infiltration of inflammatory cells and fat vacuole presence. The immunohistochemical examination showed increased expression of PPAR𝛾�, and decreased expression of NF-κB and caspase-3 to some extent when compared with the HFD group.
When reviewing the results of the bee bread, salvia officinalis, and HFD/ND administrations under the present study, we find that all have a significant effect on ameliorating hormonal disturbance, folliculogenesis defects, inflammatory responses, whether systemically or locally, and histological and immunohistochemical changes. In addition to improving the lipid profile, blood glucose, and body weight. with some restriction to the HFD/ND group as the improvement in bodyweight, the inflammatory response, and the percent of the estrous cycle regularity not as that observed in both bee bread and salvia officinalis. By comparing the three supplements, it was observed that the bee bread outperformed salvia officinalis and HFD/ND in improving all these biochemical and molecular markers measured in the blood and tissue, as well as the histological and immunohistochemical changes.